4-Methylmorpholine → 2-{4-[2-(2-Tert-butoxycarbonylamino-2-methyl-propionylamino)-3-(4-fluorophenyl)propionyl]-3-cyclopropylmethyl-2-oxo-piperazin-1-yl}-3-naphthalen-2-yl-propionic acid methylester

HRID 720173Notes

Reaction equation

HRID 720173 reaction equation
[CH3:1][O:2][C:3](=[O:39])[CH:4]([N:16]1[CH2:21][CH2:20][N:19]([C:22](=[O:33])[CH:23]([NH2:32])[CH2:24][C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[CH:18]([CH2:34][CH:35]2[CH2:37][CH2:36]2)[C:17]1=[O:38])[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1.[C:40]([O:44][C:45]([NH:47][C:48]([CH3:53])([CH3:52])[C:49](O)=[O:50])=[O:46])([CH3:43])([CH3:42])[CH3:41].ON1C2C=CC=CC=2N=N1.CN1CCOCC1.CN(C)CCCN=C=NCC>CN(C=O)C>[CH3:1][O:2][C:3](=[O:39])[CH:4]([N:16]1[CH2:21][CH2:20][N:19]([C:22](=[O:33])[CH:23]([NH:32][C:49](=[O:50])[C:48]([NH:47][C:45]([O:44][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:46])([CH3:53])[CH3:52])[CH2:24][C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)[CH:18]([CH2:34][CH:35]2[CH2:37][CH2:36]2)[C:17]1=[O:38])[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 724065532-{4-[2-Amino-3-(4-fluorophenyl)propionyl]-3-cyclopropylmethyl-2-oxo-piperazin-1-yl}-3-naphthalen-2-yl-propionic acid methylester

Product 1

HCID 695880882-{4-[2-(2-Tert-butoxycarbonylamino-2-methyl-propionylamino)-3-(4-fluorophenyl)propionyl]-3-cyclopropylmethyl-2-oxo-piperazin-1-yl}-3-naphthalen-2-yl-propionic acid methylester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-{4-[2-amino-3-(4-fluorophenyl)propionyl]-3-cyclopropylmethyl-2-oxo-piperazin-1-yl}-3-naphthalen-2-yl-propionic acid methylester, 25, (37 mg, 0.068 mmol) in DMF (1 mL) are added 2-tert-butoxycarbonylamino-2-methyl-propionic acid (202 mg, 0.079 mmol), 1-hydroxybenzotriazole (20 mg, 0.148 mmol), N-methylmorpholine (41 mg, 0.41 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (16 mg, 0.083 mmol) consecutively. The reaction mixture is stirred for 3 hours, quenched with aqueous NH4Cl and extracted several times with ethyl acetate. The combined extracts are dried over Na2SO4, filtered and concentrated in vacuo to a residue which is purified over silica gel (CH2Cl2/CH3OH, 13:1) to afford the desired product.

Workup

  1. customquenched with aqueous NH4Cl
  2. extractionextracted several times with ethyl acetate
  3. dry with materialThe combined extracts are dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo to a residue which
  6. customis purified over silica gel (CH2Cl2/CH3OH, 13:1)

Sources & evidence

ORD record
ord-7420d4e6cdeb451ab7e110b5ff8c9e65
Source dataset
uspto-grants-2006_11
Patent number
US07132539B2

Reaction notes

Loading…